Fig. 5. A947-mediated SMARCA2 degradation synergizes with MCL1 inhibition.

a Cell viability in 4 SMARCA4 mutant NSCLC cell lines measured across a small-molecule library of 723 compounds screened as a dose-response in the presence or absence of 100 nM A947 for 5 days. Data are plotted as the difference in the concentration required to inhibit growth by 50% (ΔIC₅₀) upon −/+ A947 treatment. Two separate MCL1 inhibitors are annotated in red. b Treatment of a representative SMARCA4-mutant cell line (NCI-H1793) with a 9 × 9 matrix titration of A947 with the MCL1 inhibitors, AMG-176 (upper plot) and S63845 (lower plot). Heatmaps depict activity in excess of the Bliss independence model to describe synergistic drug interactions (excess volume). c Live cell monitoring of apoptosis in SMARCA4-mutant NCI-H1944 (left graph) and NCI-H838 (right graph) cells grown in the presence of Caspase-3/7 Green Dye upon treatment with 100 nM A947 and/or 1 μM AMG-176. Data are presented apoptotic object count (mean ± s.d) in triplicate cultures. Significance was calculated by a two-, unpaired t-test; p = 0.0078 (NCI-H1944), p = 0.0002 (NCI-H838). Source data are provided as a Source Data file.